Abstract
Background/Aim: We report a case of inoperable thoracic chordoma successfully treated with carbon-ion radiotherapy (C-ion RT).
Case Report: A 65-year-old male patient underwent computed tomography for evaluation of a benign thyroid nodule and was incidentally diagnosed with thoracic chordoma without metastasis. A physical examination revealed increased tendon reflexes in the lower extremities. Magnetic resonance imaging revealed a tumour measuring 52 mm in maximum diameter, located from the seventh cervical to the third thoracic vertebrae, compressing a wide area of the spinal cord. The patient was unsuitable for surgery due to the high risk of severe postoperative neurological dysfunction. The patient received C-ion RT at a total dose of 64.0 Gy (relative biological effectiveness), delivered in 16 fractions. The patient completed C-ion RT as scheduled; however, the patient experienced transient Lhermitte’s sign, classified as grade 1 acute neuropathy, during treatment. The patient is alive 96 months after C-ion RT initiation with no evidence of local recurrence or distant metastasis, remains ambulatory, and has developed no grade 2 or higher toxicities other than the grade 1 neuropathy that was present prior to the initiation of C-ion RT.
Conclusion: We observed a favourable local response with manageable toxicity in a patient with thoracic chordoma treated with C-ion RT. Although this is a single-case report, our findings suggest that C-ion RT could be considered a viable treatment option for thoracic chordomas.
Introduction
Chordoma is a rare malignant tumour that occurs in one in one million people and is more common in males, with an age of onset of 50-60s (1, 2). It probably originates from the remnants of the primitive notochord and is found in the skull base and spine, with 50-60% in the sacral region, 25-35% in the skull base, 10% in the cervical spine, and 5% in the thoracic and lumbar spine (3, 4). Although the mainstay of curative treatment for chordomas is resection, in some cases surgery may not be indicated depending on the patient’s condition, such as anatomic problems, complications, or severe postoperative loss of function (5).
Carbon-ion (C-ion) radiotherapy (RT) has physical and biological advantages over X-ray RT in terms of higher dose localisation properties and higher cell-killing effects. Higher dose localisation properties owing to the distal tail-off by the Bragg peak and the sharp lateral penumbra enable higher-dose administration to tumours while sparing normal tissues. With higher cell-killing effects, C-ion beams have a high linear energy transfer, demonstrating a superior ability to induce cell death in radioresistant and hypoxic cells compared with X-rays. Owing to these characteristics, C-ion RT has been reported to have favourable clinical results for the treatment of bone and soft tissue sarcomas, including chordomas (6-10). However, reports of C-ion RT for thoracic chordomas, and long-term observations of C-ion RT for thoracic chordomas are lacking. Herein, we report our experience with the favourable clinical results of C-ion RT for thoracic chordomas.
Case Report
Patient. A 65-year-old Japanese male patient underwent a computed tomography (CT) for the evaluation of a benign thyroid nodule and was incidentally diagnosed with thoracic chordoma. The patient was referred to the Gunma University Heavy Ion Medical Centre (GHMC) for C-ion RT by the Department of Orthopaedics. The patient had a locally advanced disease and was unsuitable for surgery because of the high risk of severe postoperative neurological dysfunction. According to the Eastern Cooperative Oncology Group, the patient’s performance status score was 0. A physical examination revealed increased tendon reflexes in the lower extremities. Magnetic resonance imaging (MRI) revealed a tumour measuring 52 mm in maximum diameter, located from the seventh cervical to third thoracic vertebrae, with severe spinal cord compression, which showed good contrast on gadolinium-enhanced T1-weighted images (Figure 1). 2-Deoxy-2-[18F]fluoroD-glucose (FDG)-positron emission tomography (PET)/CT showed abnormal FDG uptake [the maximum standardized uptake value (SUVmax) was 3.5] in the lesion. None of the imaging modalities showed evidence of lymph node or distant organ metastases. A CT-guided needle biopsy confirmed the diagnosis of chordoma. The patient was staged at stage IB (clinical T2bN0M0), according to the 8th edition of the Union for International Cancer Control/American Joint Committee on Cancer TNM staging system. The medical history included a goitre and prostatic hyperplasia. Given the patient’s ineligibility for surgery, C-ion RT was selected as a local treatment approach. Informed consent for this treatment was obtained from the patient before the initiation of therapy, and the Ethics Committee of the Gunma University Graduate School of Medicine approved this case report.
Magnetic resonance imaging (MRI) and fluorodeoxyglucose (FDG)-positron emission tomography (PET) showing thoracic chordoma before the initiation of carbon-ion radiotherapy. The tumour was located on the seventh cervical to third thoracic vertebrae, with contrast enhancement and abnormal FDG uptake (the maximum standardized uptake value was 3.5). The size of the tumour was 41×27×52 mm. (A) Axial MRI of the gadolinium-enhanced T1-weighted image. (B) Axial MRI of the diffusion-weighted image. (C) Axial MRI of the apparent diffusion coefficient image. (D) Axial FDG-PET.
Carbon-ion radiotherapy. In the C-ion RT, a heavy-ion accelerator at the GHMC generates C-ion beams. Beam energies of 380 MeV/u in the 225-degree beam and 290 MeV/u in the 315-degree beam were selected based on the tumour depth. C-ion RT doses were expressed as the relative biological effectiveness (RBE)-weighted dose [Gy (RBE)], defined as the physical dose multiplied by the RBE of the C-ion beams (11). Treatment-planning CT images and contrast-enhanced MRI scans were merged to delineate the target precisely. The gross tumour volume (GTV) and clinical target volume (CTV) were determined. The CTV was obtained using a margin with an anatomical compartment of the muscle or bone or at least a 5-mm margin around the GTV to include microscopic diseases. When the CTV overlapped with an organ at risk (OAR) (e.g., spinal cord), the margin was reduced accordingly. The planning target volume (PTV) included the CTV with at least a 3-mm margin for possible positioning errors. When the PTV overlapped the OAR, the margin decreased accordingly. The patient received 64.0 Gy (RBE) in 16 fractions over four weeks [4.0 Gy (RBE) per fraction]. Dose constraints were defined as the dose delivered to a 1 cm3 volume (D1cc) of <30 Gy (RBE) to the spinal cord. In the actual treatment plan, D1cc was 25.9 Gy (RBE). Figure 2 shows the dose distribution of C-ion RT. The patient’s position was verified using digital orthogonal X-ray images and reference images that were digitally reconstructed based on the planning CT for daily patient position matching. Tumour response was assessed using the Response Evaluation Criteria in Solid Tumours (version 1.1) and PET Response Criteria in Solid Tumours (12, 13). Toxicities were assessed using the Common Terminology Criteria for Adverse Effects (version 4.0) (14).
Dose distribution of carbon-ion radiotherapy. (A) Axial image. (B) Sagittal image. Highlighted are 60 Gy (RBE) (red), 50 Gy (RBE) (orange), 40 Gy (RBE) (yellow), 30 Gy (RBE) (light green), 20 Gy (RBE) (green), 10 Gy (RBE) (blue), and 5 Gy (RBE) (purple) isodose curves.
Clinical result. The patient completed a C-ion RT schedule. During C-ion RT, the patient developed transient Lhermitte’s sign as grade 1 acute neuropathy, which improved with the oral administration of steroids. Three months after the initiation of C-ion RT, the tumour size was slightly reduced and spinal cord compression decreased (Figure 3). The SUVmax of the tumour decreased from 3.5 to 2.2 and a complete metabolic response was observed on FDG-PET (Figure 4). The tumour continued to slowly shrink until 78 months after C-ion RT but remained within the range of stable disease as the tumour response. The patient is alive 96 months after C-ion RT initiation with no evidence of local recurrence or distant metastasis, remains ambulatory, and has developed no grade 2 or higher toxicities other than Grade 1 neuropathy prior to the initiation of C-ion RT.
Treatment response of carbon-ion radiotherapy (C-ion RT) assessed using magnetic resonance imaging. The white arrows show the tumour. (A) Before C-ion RT. (B) Three months after C-ion RT. The tumour shows shrinkage and spinal cord decompression. (C) Twenty-four months after C-ion RT. (D) Thirty-six months after C-ion RT. (E) Forty-eight months after C-ion RT. (F) Sixty months after C-ion RT. (G) Seventy-eight months after C-ion RT.
Treatment response of carbon-ion radiotherapy (C-ion RT) assessed using fluorodeoxyglucose-positron emission tomography (FDG-PET). (A) Before C-ion RT. The red circle shows the tumour with abnormal FDG uptake (the maximum standardized uptake value (SUVmax) was 3.5). (B) Three months after C-ion RT. The red circle shows the disappearance of abnormal FDG uptake (SUVmax was 2.2). (C) Twenty-four months after C-ion RT. The red circle shows the no recurrence of the tumour (SUVmax was 2.1).
Discussion
In this case of thoracic chordoma treated with C-ion RT, we observed favourable clinical outcomes with long-term local efficacy and no severe toxicities, although the tumour has severe spinal cord compression. The treatment strategies for patients with thoracic chordomas who are unsuitable for surgery remain debatable. Furthermore, data on the efficacy and safety of C-ion RT are currently limited. We believe that our findings contribute to the development of effective treatment strategies for inoperable thoracic chordomas.
Regarding the treatment of chordomas, surgery is the first line of consideration in operable cases, while for inoperable cases treatment remains controversial. In a previous study of radiotherapy for skull base chordomas, progression-free survival following proton beam therapy (PBT) was superior to X-ray RT for relatively small tumours (median tumour volume <50 ml), and a comparison of PBT and C-ion RT (tumour or target volume <100 ml) was reported to have comparable local control (LC) and overall survival (OS) (15, 16). Additionally, C-ion RT shows favourable clinical results for upper cervical chordomas, with 5-year LC and OS rates of 75% and 68%, respectively (17). In the initial treatment of sacral chordoma, which targets relatively large tumours, the 3-year LC rate in PBT (median tumour volume 166 ml) is 90%, and the 5-year LC rate in C-ion RT (median CTV 523 ml) is 89% (18, 19). Thus, radiotherapy, especially C-ion RT, which has high biological efficacy for radioresistant tumours, may be considered a local treatment option for skull base, cervical, and sacral chordomas; however, no sufficient quality reports were identified on thoracic and lumbar spine chordomas. Although there have been reports regarding molecular-targeted therapy, systemic therapy is generally used in patients with metastatic conditions (20). Therefore, C-ion RT appears to be a favourable local treatment option for patients with inoperable chordomas.
Chordomas progress relatively slowly and long-term follow-up is important. Till today no study has reported of long-term follow-up after C-ion RT for thoracic chordomas, and this is the first case report with a long-term follow-up of 96 months. In the present case, although the tumour was primarily located in the thoracic spine and compressed a wide area of the spinal cord, long-term observation after C-ion RT showed no neurological toxicities. Although the dose constraints for the spinal cord in C-ion RT are unclear, D1cc <30 Gy, which was used in the report by Aoki et al. (17) and in our study, may serve as a reference value. Additionally, because this case was a bone tumour, we believe that the bone-matching technique with X-rays performed in the actual treatment was sufficient to reproduce the treatment plan in terms of clinical results.
Conclusion
We encountered a case of thoracic chordoma treated with C-ion RT with favourable local effects and acceptable toxicities. Our findings suggest that C-ion RT is a potential treatment option for patients with inoperable thoracic chordomas.
Footnotes
Authors’ Contributions
Conceptualisation: D. I., S. S., Y. M., and M. O.; Investigation: D. I., S. S., Y. M., and M. O.; Resources: D. I., S. S., Y. M., M. O., and H. K.; Patient treatment: D. I., S. S., M. O., H. K., and T. O.; Writing – original draft preparation: D. I., S. S., and Y. M.; Writing – review and editing: D. I., S. S., Y. M., M. O., Y. Y., K. S., H. K., and T. O.; Visualisation: D. I., S. S., Y. M., and Y. Y.; Supervision: T.O.; Project administration: M.O. and T.O.
Conflicts of Interest
Tatsuya Ohno received funding from Hitachi (Japan). The other Authors declare no conflicts of interest in relation to this report.
Funding
This study received financial support from the Gunma University Heavy Ion Medical Centre for the publication of this article.
- Received March 2, 2025.
- Revision received March 18, 2025.
- Accepted March 19, 2025.
- Copyright © 2025 The Author(s). Published by the International Institute of Anticancer Research.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).
